BACKGROUND. Whereas normal epithelial cells cannot grow under anchorage independent conditions in vitro, KRAS transformed cancer cells can proliferate to for a tumor sphere under these same conditions. This ability of the KRAS oncogene to drive anchorage independent growth is a hallmark of malignant transformation. PURPOSE. In this project we aim to study how the KRAS oncogene enables cancer cells to proliferate under anchorage independent conditions. We aim to study KRAS mediated signal transduction pathways and understand how they regulate cell cycle and cell survival. ACCOMPLISHMENT. We have identified KRAS mutant cancer cell lines that are strictly dependent on KRAS for anchorage independent growth. We have identified distinct features of oncogenic KRAS signaling in tumor spheroid culture that suggest novel mechanisms by which the KRAS oncogene uses to enable cell survival and cell proliferation in the anchorage independent setting.